Targeting angiotensinogen with RNA-based therapeutics

Liwei Ren, Katrina M. Mirabito Colafella, Dominique M. Bovée, Estrellita Uijl, A. H.Jan Danser

Research output: Contribution to journalReview ArticleResearchpeer-review

20 Citations (Scopus)

Abstract

Purpose of reviewTo summarize all available data on targeting angiotensinogen with RNA-based therapeutics as a new tool to combat cardiovascular diseases.Recent findingsLiver-targeted, stable antisense oligonucleotides and small interfering RNA targeting angiotensinogen are now available, and may allow treatment with at most a few injections per year, thereby improving adherence. Promising results have been obtained in hypertensive animal models, as well as in rodent models of atherosclerosis, polycystic kidney disease and pulmonary fibrosis. The next step will be to evaluate the optimal degree of suppression, synergy with existing renin-angiotensin-aldosterone system blockers, and to determine harmful effects of suppressing angiotensinogen in the context of common comorbidities, such as heart failure and chronic kidney disease.SummaryTargeting angiotensinogen with RNA-based therapeutics is a promising new tool to treat hypertension and diseases beyond. Their long-lasting effects are particularly exciting, and if translated to a clinical application of at most a few administrations per year, may help to eliminate nonadherence.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalCurrent Opinion in Nephrology and Hypertension
Volume29
Issue number2
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Angiotensin
  • Angiotensinogen
  • Antisense oligonucleotides
  • Drug adherence
  • Renin
  • RNA interference

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